Optimizing the Effectiveness of Selective Serotonin Reuptake Inhibitors (SSRIs) in Treatment-Resistant Depression

• ClinicalTrials.gov Identifier: NCT00093847
• Recruitment Status: Completed
• First Posted: October 8, 2004
• Results First Posted: October 13, 2014
• Last Update Posted: October 13, 2014
• Sponsor: Massachusetts General Hospital
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): George I. Papakostas, Massachusetts General Hospital

Study Description

Brief Summary:

This study will determine the effectiveness of adding S-adenosyl methionine to antidepressant drug treatment in reducing depressive symptoms in depressed people who have not responded to antidepressants alone.

Condition or disease	Intervention/treatment	Phase
Depression	Drug: S-adenosyl methione (SAMe); Drug: Placebo	Phase 2

Detailed Description:

Some people with depression do not respond well to antidepressant treatment. S-adenosyl methionine (SAMe) is a naturally occurring compound that may have antidepressant effects. SAMe may also enhance the effectiveness of other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). This study will determine the effectiveness of oral SAMe in enhancing the effects of SSRIs in patients currently not responding to SSRI treatment.

This study will last 6 weeks. No follow-up visits will occur. Participants will be randomly assigned to add either oral SAMe or placebo to their existing SSRI regimen for 6 weeks. Depression scales and self-report questionnaires regarding depressive symptoms will be used to assess participants at the end of the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 73 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: S-adenosyl Methionine (SAMe) Augmentation of Selective Serotonin Reuptake Inhibitors (SSRIs) for Treatment-Resistant Depression (TRD)
• Study Start Date: May 2004
• Actual Primary Completion Date: February 2009
• Actual Study Completion Date: February 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 Oral SAMe Tosylate; Participants receiving the oral SAMe tosylate	Drug: S-adenosyl methione (SAMe); Oral SAMe tosylate, up to 1600 mg per day for 6 weeks; Other Name: Oral SAMe tosylate
Placebo Comparator: 2 Oral Placebo Pill Twice Daily; Participants receiving placebo	Drug: Placebo; Placebo to be taken daily for 6 weeks; Other Name: Pill identical in appearance to drug but placebo

Outcome Measures

Primary Outcome Measures :

1. Hamilton Depression Rating Scale Remission Rates [ Time Frame: Measured at Week 6 ]
   The proportion of remitters for SAMe versus placebo was 46.1% versus 17.6%. Remission is defined as a final score of 7 or less on Hamilton Depression Rating Scale 17 item .

Secondary Outcome Measures :

1. HDRS17 Responders [ Time Frame: Measured at Week 6 ]
   35.8% versus 11.7%. Response is defined as a 50 percent or more score reduction on on Hamilton Depression Rating Scale 17 item .

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Major depressive disorder
• Use of an SSRI for at least 6 weeks prior to study entry with partial or no response

Exclusion Criteria:

• History of psychosis
• Allergy to SAMe
• Alcohol or drug abuse in the past 3 months prior to study entry

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: George I. Papakostas, MD; Massachusetts General Hospital

More Information

Publications of Results:

Papakostas GI, Mischoulon D, Shyu I, Alpert JE, Fava M. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry. 2010 Aug;167(8):942-8. doi: 10.1176/appi.ajp.2009.09081198. Epub 2010 Jul 1.

Other Publications:

Papakostas GI, Alpert JE, Fava M. S-adenosyl-methionine in depression: a comprehensive review of the literature. Curr Psychiatry Rep. 2003 Dec;5(6):460-6. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mischoulon D, Alpert JE, Arning E, Bottiglieri T, Fava M, Papakostas GI. Bioavailability of S-adenosyl methionine and impact on response in a randomized, double-blind, placebo-controlled trial in major depressive disorder. J Clin Psychiatry. 2012 Jun;73(6):843-8. doi: 10.4088/JCP.11m07139. Epub 2012 May 15.

Dording CM, Mischoulon D, Shyu I, Alpert JE, Papakostas GI. SAMe and sexual functioning. Eur Psychiatry. 2012 Aug;27(6):451-4. doi: 10.1016/j.eurpsy.2011.01.003. Epub 2011 Mar 12.

• Responsible Party: George I. Papakostas, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00093847
• Other Study ID Numbers: K23MH069629 ( U.S. NIH Grant/Contract ); K23MH069629 ( U.S. NIH Grant/Contract )
• First Posted: October 8, 2004
• Results First Posted: October 13, 2014
• Last Update Posted: October 13, 2014
• Last Verified: October 2014

Keywords provided by George I. Papakostas, Massachusetts General Hospital:

Selective Serotonin Reuptake Inhibitors; S-adenosyl Methionine; SSRI; SAMe

Additional relevant MeSH terms:

Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Behavioral Symptoms; Mood Disorders; Mental Disorders